Updates from the National Antimicrobial Committee (NAC) Updates 2018.pdf · Updates from the...
Transcript of Updates from the National Antimicrobial Committee (NAC) Updates 2018.pdf · Updates from the...
Updates from the National Antimicrobial Committee (NAC)
Dr. Anne-Marie Van den Abeele, AZ St Lucas, GentDr. Bénédicte Lissoir, GHdC, Charleroi
Dr. Kris Vernelen, ISP-WIV, Brussel
Content• Fosfomycin susceptibility testing
• Trimethoprim-sulfamethoxazole and Stenotrophomonas maltophilia
• Survey satisfaction NAC panel 2016
Fosfomycin: introduction
• Streptomyces fradiae (1969, Spain)• Low molecular weight• Water soluble: good tissue diffusion• Drug formulation:
• Dosage:
- Fosfo-tromethamine/trometamol (soluble salt ) oral use- Fosfo-calcium oral use (less good bioavailability)- Fosfo-disodium salt intravenous use
Usual dosage IV: 3x4g/dHigh dosage IV: 3x8g/d
Fosfomycin: spectrum of activity
Broad spectrum activity, bactericidal (MBC≈ MIC)
Gram + - Staphylococcus aureus (MSSA, MRSA)- (Streptococci, Enterococci)
Gram -- Escherichia coli- Proteus mirabilis- (K. pneumoniae, Enterobacter spp.)- Pseudomonas aeruginosa
Fosfomycin: resistance mechanisms
- Plasmidic: Inactivating enzymes- Metallo enzymes: FosA, FosB, FosXtransferable
- Kinases: FomA, FomB
- Chromosomal: Mutations in uptake system genes(transporters: GlpT, UhpT)
- Reduced affinity to target (MurA) (natural resistance)Staphylococcus saprophyticus, (S. capitis), Morganella morganii, Acinetobacter spp, Burkholderia cepacia, Stenotrophomonas maltophilia, Anaerobes
! No cross resistance with other classes of antibiotics! Resistant mutants less virulent (fitness cost)! High frequency of mutations during treatment
Fosfomycin AST (1)
EUCAST (Enterobacteriaceae / Staphylococci): S < 32 µg/ml; R > 32 µg/ml
CLSI (Enterobacteriaceae): S < 64 µg/ml; I= 128 µg/ml; R ≥ 256 µg/ml
Only urinary E. coli
No breakpoints (Pseudomonas aeruginosa) EUCAST: potential use of ECOFF (MIC =128 mg/l) for use in combination
therapyMiscellaneous agents MIC breakpoint
(mg/L)Disk
content (µg)
Zone diameter breakpoint
(mm)
Notes Numbered notes relate to general comments and/or MIC breakpoints. Lettered notes relate to the disk diffusion method.
S ≤ R > S ≥ R <Chloramphenicol - - - - 1. Colistin MIC determination should be performed with broth microdilution. Quality control must be performed with both a
susceptible QC strain (E. coli ATCC 25922 or P. aeruginosa ATCC 27853) and the colistin resistant E. coli NCTC 13846 (mcr-1 positive).2. Agar dilution is the reference method for fosfomycin. MICs must be determined in the presence of glucose-6-phosphate (25 mg/L in the medium). Follow the manufacturers' instructions for commercial systems. Infections caused by wild type isolates (ECOFF: MIC 128 mg/L; corresponding zone diameter 12 mm using the disk potency and reading instructions for E. coli) have been treated with fosfomycin in combination with other agents.
A. Use an MIC method (broth microdilution only).
Colistin1 2 2 NoteA NoteA
Daptomycin - - - -
Fosfomycin iv2 - - - -
Fosfomycin oral2 - - - -
Fusidic acid - - - -Metronidazole - - - -Nitrofurantoin (uncomplicated UTI only) - - - -Nitroxoline (uncomplicated UTI only) - - - -Rifampicin - - - -Spectinomycin - - - -Trimethoprim (uncomplicated UTI only) - - - -Trimethoprim-sulfamethoxazole - - - -
EUCAST• Reference method: Agar dilution
• Alternatives?- Disk diffusion (only E. coli, other Enterobacteriaceae use MIC method)
- Broth microdilution- Automated AST systems
• ALL techniques:+ glucose-6-phosphate (G6P) (25 mg/L in medium)
Fosfomycin AST (2)
Fosfomycin AST: disk diffusion
• Disk diffusion
1. Use a MIC method (broth microdilution as alternative for agar dilution?)2. Fosfomycin 200 µg disks must contain 50 µg glucose-6-phosphate.3. Zone diameter breakpoints apply to E. coli only. For other Enterobacteriaceae, use an MIC method.4. Ignore isolated colonies within the inhibition zone (see pictures).
Fosfomycin AST: BMD (1)broth microdilution
Presence of « outliers » (skip wells): <-> growth of resistant mutants
• Broth microdilution
Fosfomycin AST: BMD(2)broth microdilution
Fosfomycin +G6P
4 mg/l
8 mg/l
16 mg/l =MIC
32 mg/l
64 mg/l
128 mg/l
K. pneumoniae
Fosfomycin: use of automated AST systems
FDA/ISO cleared?Quality validation studies?
Yes: E. coli, low resistance rates (2-5%) Yes: S. aureus, low resistance rates (2-5%)
No: K. pneumoniae, high resistance rates (20-30%)No: Pseudomonas aeruginosa, no breakpoints
Trimethoprim-sulfamethoxazole and Stenotrophomonas maltophilia
Specific reading instructions
BVIKM-SBIMC symposium 29th March 2018Dr Bénédicte Lissoir
National Antibiotic Committee
Stenotrophomonas maltophilia
• Aerobic non fermentative Gram-negativebacterium
• Ubiquitous environmental microorganism• Often associated with colonization• Opportunistic pathogen
(immunocompromised patients and patients with cystic fibrosis)
Intrinsic resistance – S.maltophilia
www.eucast.org
Trimethoprim-sulfamethoxazole
• Sulfonamides / trimethoprim (diamino pyridine)
• Bactericidal (Gram + & Gram -)• Blocks 2 consecutive steps in the bio-
synthesis of nucleic acids and proteins of bacteria• Uses : Pneumocystis jiroveci pneumonia, bacterial meningitis (not specific
enough!?), chronic bronchitis, Shigellosis, traveler’s diarrhea, urinary tract infections, Stenotrophomonas treatment, nocardiosis …
– Wide variety of resistance mechanisms : alteration of permeability, overexpression of efflux pump systems, modification of targetenzymes (DHPS <-> sulfonamide; DHFR <-> trimethoprim),…
DHPS
DHFR
Trimethoprim - sulfamethoxazole
• Natural resistance to trimethoprim –sulfamethoxazole : – Pseudomonas aeruginosa– Anaerobic microorganisms– Campylobacter sp– Helicobacter pylori– Mycobacteria– Mycoplasma, Ureaplasma– Neisseria sp– Borrelia sp– Treponema sp.
EUCAST - AST recommendations for S. maltophilia
CA-SFM and CLSI AST recommendations for S. maltophilia
• Antibiotics other than cotrimoxazole to betested:
French committee (CA-SFM, 2017 v2.0)
CLSI 2017, M100-S27
- Ticarcillin / Clavulanic acid- Ceftazidime- Levofloxacine- Minocycline (tigecycline ?)
Disc diffusion criteria (CA-SFM,CLSI): only for levofloxacin, minocycline
www.eucast.org
Survey satisfaction NAC panel 2016
Rue Juliette Wytsmanstraat 14 | 1050 Brussels | Belgium
T +32 2 642 51 11 | F +32 2 642 50 01 | email: [email protected] | www. wiv-isp.be
Quick reminder
The NAC developed a challenge panel: including both Gram-negatives and Gram-positives Covering most important resistance mechanisms
For the implementation of EUCAST breakpoints or EUCAST methods in the clinical laboratories
Panel send out to requesting laboratories as fromApril 2016
Response rate
Send out: 24/07/17
Deadline: 11/09/17
Reminder: 21/09/17
Final response rate january 18: 44/71 (62%)
7 labs: not yet used the panel; storage for future use
Appreciation & use
Median score : 8 ( 4 - 10)
Use:17 labs : 1 occasion14 labs : > 1 occasion
Purpose
Validation of existing method & guidelines: 13Implementation of new guidelines: 5Implementation of new method & validation m/g: 5Implementation of new method: 4Implementation of new m/g & validation m/g: 4Implementation of new method & new guidelines: 2Other: 4
Storage
Original panel RT: 1Original panel refrigerator: 3Original panel freezer: 13Aliquots freezer: 25Original panel & aliquots freezer: 1
Problems growth/contamination (35 labs)
21 labs: noneProblem strains:
S. pneumoniae (strain #50): 9S. pneumoniae (strain #48): 7S. pneumoniae (strain #52): 6S. agalactiae (strain #35): 3S. aureus (strain #53): 3P. aeruginosa (str #3) – K. pneumoniae (str #15): 1
Problems identification (35 labs)
29 labs: noneProblem strains:
E. coli (str #7) identified as E. aerogenes (2 labs)P. aeruginosa (str #4) identified as E. aerogenes S. pneumoniae (str #48) identified as S. mitis/pneumoniaeS. aureus (str #53) identified as S. capitis/warneri
Problems antibiogram (35 labs)
28 labs: noneStr 4# (P. aeruginosa): many discordances, needs to
be retestedStr#L2 (E. coli): levo I i.o. SStr#38 (S. agalactiae): clinda R i.o. S (Vitek expert
system)Str #11 E. aerogenes genta R i.o. S & str #38
(S. agalactiae): clinda R i.o. SStr #11 E. aerogenes (cefur R) & str 24 C. koseri (cefur
S) but EUCAST 2015: no breakpoints
Suggestions for future panels
38 labs interested – 33 interested in collaboratingColistin-resistant Enterobactericeae: 25 labsLinezolid -resistant S. aureus: 18 labsLinezolid-resistant Enterococcus: 17 labsTigecycline-resistant Acinetobacter: 10 labsOther combinations germ/AB: 8 labs
Lessons learned
Information about storage
Inoculate certain strains upon reception (e.g. pneumococci)
The future
Then NAC considers a new/updated panel
Members of the bureau of the National Antimicrobial Committee (NAC)
• Olivier Denis (ULB- Chirec, BAPCOC, BVIKM-SBIMC)• Youri Glupczynski (CHU UCL Namur, Godinne)• Bénédicte Lissoir (GHdC – Charleroi)• Koen Magerman (Jessa Ziekenhuis, Hasselt - BAPCOC)• Pierrette Melin (CHU Liège)• Hector Rodriguez-Villalobos (St Luc Bruxelles, UCL, SBIMC)• Anne-Marie Van den Abeele (AZ St Lucas Gent)• Jan Verhaegen (UZ, Leuven, BVIKM-SBMIC) • Kris Vernelen (ISP-WIV)• Erlangga Yusuf (UZ Antwerpen)